Pharmacogenomics cs at at the NIH Simona Volpi, PhD Division of - - PowerPoint PPT Presentation

Pharmacogenomics cs at at the NIH

Simona Volpi, PhD Division of Genomic Medicine, NHGRI Genomic Medicine X Meeting May 2nd, 2017

Pharmacogenomics at the NIH Meeting

• December 14, 2016
• Organized by NHGRI’s Division of Genomic Medicine staff
• Representatives from 12 NIH ICs presented their ICs’ involvement in

PGx research

• Goal: to survey the landscape of NIH-funded PGx research to help

coordinate IC efforts and inform the May 2017 GM X meeting

• Information included: resources developed, programs and consortia

efforts, award mechanisms

Outline

• Resources
• Clinical trials
• Network Efforts
• Meeting outcome

Resources

NCBI supports 4 main PGx resources:

• Genomic Test Registry (GTR)
• international registry of available genetic tests
• ~5,000 orderable tests
• ClinVar
• clinical significance of genomic sequence variations

and their relationship to phenotypes

• MedGen
• phenotype resource for information on conditions

with genetic component

• Medical Genetic Summaries
• structured reviews about genetic variants and drug

responses

Resources (cont’d)

Supported by NHGRI:

• IGNITE Spark Toolbox
• to help clinicians incorporate genomics into their practices, researchers study the

best ways to use genomics in healthcare and educators provide genomic training to future healthcare providers.

• Sequence and Phenotype Integration Exchange (SPHINX)
• a web-based tool for exploring data for hypothesis generation, especially around

drug response implications of genetic variation across the eMERGE PGx cohort.

Supported by NIDDK:

• Type 2 Diabetes Knowledge Portal
• goal is to increase the number of new diagnostics and therapies for patients while

reducing the time and cost of developing them.

Resources (cont’d)

Supported by NIGMS:

• Clinical Pharmacogenetics Implementation

Consortium (CPIC) - NHGRI

• Pharmacogenomics Knowledgebase (PharmGKB)
• PGRN-PiLS
• The PGx iPSC Library and Service (PiLS) is the first resource
• f its kind that provides PGRN members the ability to

access and contribute towards iPSC library for pharmacogenomics research. ​

• F-CAP (Functionalization of Variants in Clinically

Actionable Pharmacogenes)

• Pharmacogenetics of Membrane Transporters

Database (PMT)

• goal is to understand the genetic basis for variation in

response for drugs that interact with membrane transporters.

Clinical Trials

Supported by NCI:

• Adjuvant Lung Cancer Enrichment Marker Identification and

Sequencing Trials (ALCHEMIST)

• Lung-MAP
• Molecular Analysis for Therapy Choice (MATCH)

Supported by NIMH:

• Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder

(PGBD)

• Neurobiology of Treatment Responses in Major Depressive Disorder

(MDD)

Network Efforts

• Supported by NIDDK
• Drug-Induced Liver Injury Network (DILIN)
• create a registry of DILI cases
• identify clinical, immunological, and environmental risk

factors for drug- and CAM-mediated hepatotoxicity

• Supported by NIGMS (primarily)
• Pharmacogenomics Research Network (PGRN)
• lead research for discovery and translation of genomic

variation influencing therapeutic and adverse drug effects

• Supported by OD
• The Precision Medicine Initiative (PMI) hosts The All of

Us℠ Research Program.

• The National Institutes of Health Clinical Center (CC)

Network Efforts (cont’d)

• Supported by NHGRI
• Implementing Genomics in Practice (IGNITE)
• share and disseminate data from multiple sites implementing PGx testing

to contribute to the evidence base of metrics and health-related outcomes gained from using PGx information in clinical care.

• The Clinical Genome Resource (ClinGen) PGx WG
• evaluate and annotate PGx genes, develop systematic methods for

representing and depositing knowledge into ClinVar, and reconcile nomenclatures for pharmacogenomics variants. The PGx WG has proposed four categories of PGx variants to facilitate the reconciliation of PGx nomenclature.

• Electronic Medical Records and Genomics (eMERGE) PGx
• validate actionable variants in a CLIA-certified environment, and to

integrate PGx variants into EMRs for use in clinical treatment.

Ch Challenges s Identifi fied and Potential Syn ynergies s an and Collab llaboratio tions

• Standardize the PGx allelic nomenclature and relevant

phenotypes across all datasets and resources

• Identify and assess all the PGx resources currently available to

the research and clinical communities

• Reduce unproductive duplication and overlap among resources
• Population diversity remains a challenge
• ADR
• Effectiveness of pre-emptive genotyping should be assessed PGx-

wide rather than drug-by-drug or disease-by-disease

Ch Challenges s Identifi fied and Potential Syn ynergies s an and Collab llaboratio tions (cont’d)

• Costs need to be considered – pre-emptive testing
• Engaging payers for reimbursement – evidence missing?
• Translating PGx data into cancer treatments and precision
• ncology
• Immunopharmacology should be explored for applications

beyond cancer and infectious diseases

• Lack of biological markers (psychiatry)
• NIH ICs need to collaborate
• Implementation projects examples
• Share samples and databases
• Animal, iPSC models of tox and epi/genomics of drug response

Thank you!

• CC

Barry Goldspiel

• NCBI

Wendy Rubinstein

• NCI

Kelly Filipski, Min Song

• NHLBI

Antonello Punturieri

• NIAMS

Susana Serrate-Sztein, Yan Wang

• NICHD

Zhaoxia Ren

• NIDA

Jonathan Pollock

• NIDDK

Jenna Baker, Aaron Pawlyk

• NIGMS

Rochelle Long

• NIMH

Geetha Senthil

• NINDS

Vicky Whittemore

• PMI

Carolyn Hutter

NHGRI Melpi Kasapi Teri Manolio